Genetic variants in potassium channels are associated with type 2 diabetes in a Mongolian population

Abstract

Objectives Recent genome-wide association studies (GWAS) have identified more than 40 common sequence variants associated with type 2 diabetes (T2D). However, the results are not always the same in populations with differing genetic backgrounds. We evaluated a hypothesis that a North Asian population living in a geographic area with unusually harsh environmental conditions developed unique genetic risks. Methods We performed a population-based association study with 21 single-nucleotide polymorphisms (SNPs) in 9 genes selected according to the results of GWAS conducted in other populations. The study participants included 393 full-heritage Mongolian individuals, 177 diagnosed with T2D and 216 matched controls. Genotyping was performed by TaqMan methodology. Results The strongest association was detected with SNPs located within the potassium-channel coding KCNQ1 (highest OR=1.92; P=3.4×10−5) and ABCC8 (OR=1.79; P=5×10−4) genes. Genetic variants identified as strongly influencing the risk of T2D in other populations such as those in KCNJ11 or TCF7L2 genes did not show statistically significant association in Mongolia. Conclusions The strongest T2D risk-associated SNPs in Mongolians are located within 2 of 3 tested potassium-channel coding genes; accumulated variations in these genes may be related to environmental exposure to extreme cold.

Association Between KCNQ1 Gene Polymorphism and Type 2 Diabetes Mellitus: Evidence from Meta-analysis

“…The association of rs2237892 polymorphism and rising T2DM incident risk proved former study result [2,4,[7][8][9][11][12][13][14][15][16][17][21][22][23][24]27,[29][30][31]36,[39][40][41][42][43][44][45][46]. East Asian, Southeast Asian and other region`s subgroup analysis also show the association still stable（OR=1.…”

“…As the same we random report the result of meta-analysis. European Saif-Ali R,2011 [26] Fuu-Jen Tsai, 2010 [34] Fuu-Jen Tsai, 2010 [34] Qi QB, 2009 [38] Turki A, 2012 [20] Dai XP, 2012 [17] Tan JT, 2009 [39] H. Grallert, 2010[33] ID Been LF, 2011 [24] Hiroyuki Unoki, 2008 [3] van Vliet-Ostaptchouk JV,2012 [21] Cui LJ,2016 [5] Chen Z, 2010 [28] Odgerel Z, 2012 [15] …”

Common Variants in KCNQ1 Confer Increased Risk of Type 2 Diabetes and Contribute to the Diabetic Epidemic in East Asians: A Replication and Meta-Analysis

“…Two more articles were identified through searching of reference lists, while 17 articles were excluded as they did not focus on any one of the four SNPs included in our study, or contained insufficient data for analysis or the outcomes that were not T2D. Finally, 19 articles were included in the meta‐analysis (Lee et al., ; Unoki et al., ; Yasuda et al., ; Hu et al., ; Liu et al., ; Qi et al., ; Takeuchi et al., ; Chen et al., ; Han et al., ; Shu et al., ; Tan et al., ; Tsai et al., ; Xu et al., ; Yamauchi et al., ; Zhou et al., ; Saif‐Ali et al., ; Tabara et al., ; Odgerel et al., ; Yu et al., ). Figure S2 provides a summary of the literature review, and the characteristics of studies selected into the meta‐analysis are listed in Table .…”

“…Four SNPs (rs2283228, rs2237892, rs2237895, and rs2237897) were included in our study, and had been explored extensively in previous studies (Yasuda et al., ; Hu et al., ; Odgerel et al., ). Genomic DNA was extracted from peripheral leukocytes isolated from venous blood collected in K2‐EDTA tubes, using a DB‐S kit (FUJIFILM Corporation, Tokyo, Japan) according to the manufacturer's instructions.…”

Role of KCNJ11 Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus

“…Isoleucine is usually interchangeable with leucine and occasionally with valine in proteins. Of 13 studies on DM, 3 showed strong associations between this variant and T2DM 38,41,46 , whereas the remaining studies showed no association with T2DM47 [60][61][62][77][78][79][80][81][82] . In another study, the rs5215 polymorphism was associated with blood pressure among subjects with T2DM 47,93 .…”